title: Requirement for frzb and fzd7a in cranial neural crest convergence and extension mechanisms during zebrafish palate and jaw morphogenesis.
abstract: Regulation of convergence and extension by wnt-frizzled signaling is a common theme in embryogenesis. This study examines the functional requirements of frzb and fzd7a in convergence and extension mechanisms during craniofacial development. Using a morpholino knockdown approach, we found that frzb and fzd7a are dispensable for directed migration of the bilateral trabeculae, but necessary for the convergence and extension of the palatal elements, where the extension process is mediated by chondrocyte proliferation, morphologic change and intercalation. In contrast, frzb and fzd7a are required for convergence of the mandibular prominences, where knockdown of either frzb or fzd7a resulted in complete loss of lower jaw structures. Further, we found that bapx1 was specifically downregulated in the wnt9a/frzb/fzd7a morphants, while general neural crest markers were unaffected. In addition, expression of wnt9a and frzb was also absent in the edn-/- mutant. Notably, over-expression of bapx1 was sufficient to partially rescue mandibular elements in the wnt9a/frzb/fzd7a morphants, demonstrating genetic epistasis of bapx1 acting downstream of edn1 and wnt9a/frzb/fzd7a in lower jaw development. This study underscores the important role of wnt-frizzled signaling in convergence and extension in palate and craniofacial morphogenesis, distinct regulation of upper vs. lower jaw structures, and integration of wnt-frizzled with endothelin signaling to coordinate shaping of the facial form.
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States.
authors.forename: George
authors.initials: G
authors.lastname: Kamel
authors.forename: Tatiana
authors.initials: T
authors.lastname: Hoyos
authors.forename: Lucie
authors.initials: L
authors.lastname: Rochard
authors.forename: Max
authors.initials: M
authors.lastname: Dougherty
authors.forename: Yawei
authors.initials: Y
authors.lastname: Kong
authors.forename: William
authors.initials: W
authors.lastname: Tse
authors.forename: Valeriy
authors.initials: V
authors.lastname: Shubinets
authors.forename: Michael
authors.initials: M
authors.lastname: Grimaldi
authors.forename: Eric C
authors.initials: EC
authors.lastname: Liao
mesh_terms: D000818:Animals; D017209:Apoptosis; D019521:Body Patterning; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007568:Jaw / Q000196:embryology* / Q000378:metabolism; D009024:Morphogenesis; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism*; D010159:Palate / Q000254:growth & development* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000099274:Frizzled-Related Proteins
chemical_list: D006023:Glycoproteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000099274:Frizzled-Related Proteins; C554086:Wnt9a protein, zebrafish; C470289:fzd7a protein, zebrafish; C491537:nkx3-2 protein, zebrafish
keywords: Convergence extension; Cranial neural crest; Craniofacial; Wnt9a; Zebrafish; frizzled; frzb; fzd7a; wnt